Subclinical phenotypes of cardiovascular disease

The National Heart, Lung, and Blood Institute awarded The University of Texas Southwestern Medical Center $246,000 on August 5, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate sex-specific differences in subclinical cardiovascular disease phenotypes and their relationship to psychosocial stress.

The recipient will develop expertise in subclinical atherosclerosis measures and cardiovascular imaging phenotypes while examining whether chronic psychosocial stressors influence women's propensity for adverse cardiovascular outcomes through different subclinical phenotypes rather than atherosclerotic burden alone. The research leverages data from the Dallas Heart Study, a multi-ethnic cohort of 6,101 Dallas County residents recruited between 2000 and 2002, aged 18–65 years without baseline cardiovascular disease. The project seeks to understand sex differences in subclinical measures and their mediated effects on cardiovascular risk among men and women, and to identify major adverse cardiovascular events associated with psychosocial stress exposure.

Work is performed in Dallas, Texas. The award period runs from August 5, 2026, through July 31, 2028. This is a Project Grant, the standard assistance type for investigator-initiated biomedical research funded by NIH institutes.

Abstract

Although cardiovascular disease (CVD) remains the number one cause of death for both men and women in the united states, research suggests that there are SEX-specific differences in cardiovascular physiology as well as clinical presentation and prognosis of CVD. Women have less atherosclerotic risk factors and less obstructive coronary artery disease such that routine measures of subclinical atherosclerosis (e.g., coronary calcium score and aortic plaque) may not capture differences in CVD and risk of adverse cardiovascular events. While women have less atherosclerotic burden, research has shown a greater psychosocial burden and greater stress reactivity that can may present CVD risk through different subclinical phenotypes. Thus, the central hypothesis for this application is that women's propensity for adverse cardiovascular outcomes may be influenced by chronic psychosocial stressors that have implications on cardiovascular structure and cardiac remodeling rather than atherosclerotic burden. The overall goal of this project is to investigate whether psychosocial stress is associated with SEX differences in subclinical phenotypes for cardiovascular disease and whether these phenotypes, in turn, have different mediated effects of cardiovascular risk among men and women, leveraging data from the dallas heart study. Through this application, the applicant's goals are to: 1) to develop additional expertise in subclinical measures of atherosclerosis and cardiovascular imaging phenotypes; and 2) understand sexual dimorphisms of these measures in relation to psychosocial stress and major adverse cardiovascular events. This project will leverage data from the dallas heart study (DHS), a multi-ethnic (~50% african american), cohort study of 6,101 residents of dallas county, texas.16 participants were recruited between 2000-2002, aged 18-65 years, and without cardiovascular disease. Of the initial sample, 3,072 participants completed a clinical visit for cardiac imaging, and 2,485 participants (52% african american; 32% white) completed both clinical visits at baseline and follow-up (2007-2009). The scientific aims of this project are to investigate: 1) SEX differences in measures of subclinical atherosclerosis and cardiac structure and remodeling at baseline and over time; 2) examine whether the composite measure of psychosocial stress is associated with SEX differences in subclinical phenotypes of cardiovascular disease; and 3) using formal mediation analysis, calculate the percent of the association between psychosocial stress and major adverse cardiovascular events that is mediated through subclinical atherosclerosis and cardiac structure and moderated by SEX. New knowledge generated from these results may help identify whether the risk of stress on adverse cardiovascular outcomes can be identified through certain subclinical phenotypes and differences for women and men that can inform health care providers about different presentations of CVD, especially for women who tend to have less subclinical atherosclerotic disease.